DNA single-strand breaks (SSBs) are the most frequent DNA lesions arising in cells and are a major threat to cell survival and genome integrity, as indicated by the elevated genetic deletion, embryonic lethality, or neurological disease observed if single-strand break repair (SSBR) is attenuated. In particular, SSBR defects are associated with hereditary neurodegeneration in humans, as illustrated by the genetic diseases ataxia oculomotor apraxia-1 (AOA1), spinocerebellar ataxia with axonal neuropathy-1 (SCAN1), and microcephaly with early onset seizures (MCSZ). However, two major questions remain: what are the mechanisms by which SSBs trigger neurodegeneration, and to what extent do SSBs contribute to other genetic and/or sporadic neurodegenerative disease? Based on exciting new data we now propose that the impact of SSBs on neurodegeneration extends beyond rare SSBR-defective diseases to include more common motor neurone diseases (amyotrophic lateral sclerosis) and the genetically dominant spinocerebellar ataxias (SCAs). Ultimately, we suggest that SSBs might also be an etiological factor in normal human ageing. Finally, again based on new data, we propose that SSBs induce neurodegeneration by triggering over-activation of the SSB sensor protein, PARP1; thereby identifying inhibitors of this protein (currently licensed for cancer treatment) as a possible therapy for neurodegeneration. We will now address these hypotheses using a range of cutting edge molecular/cellular techniques. In particular we will (a), systematically examine all relevant amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) and spinocerebellar ataxia (SCA) proteins for involvement in the DNA damage response, (b) Identify the mechanism/s by which ALS and SCA proteins engage in the DNA damage response, (c) Identify the role of ALS and SCA proteins in the DNA damage response, and (d) Explore PARP1 as a possible therapeutic target for treatment of neurodegenerative disease.

Algae4IBD's mission is to develop commercial products for Inflammatory Bowel Disease (IBD) prevention and treatment using aquatic natural biological resources. With the emerging developments in natural product, notable success has been achieved in discovering natural products and their synthetic structural analogues with anti-inflammatory activity. However, global biodiversity remains a largely unexploited resource for natural bioactive molecules with an enormous potential for developing commercial products with public health benefits. Micro and macroalgae, found in marine and freshwater, have been identified as promising sources of bioactive compounds including small molecules and secondary metabolites with a wide range of bioactivities as an antioxidant, anti-inflammatory and cancer preventive. Consumption of algae could, therefore, provide defence against chronic inflammatory diseases such as IBD, that until date have no effective cure. This project offers nature to bedside approach, using an entire development along the value chain for a new biodiscovery therapeutic approach by developing and examining algae-based compounds for IBD patients while guaranteeing algae's biodiversity preservation. We propose innovative solutions for increasing the use of algae-based ingredients and to ensure the science-based improvement of nutritional quality and its effect on public health. The researchers, companies and hospitals involved in the different stages of the project will use the biodiversity of algae, both micro and macro, as a wide source for bioactive compounds using state-of-the-art cultivation and extraction technologies for obtaining sufficient amounts of the bio-active molecules together with novel processing protocols. It will result in novel algal-based, high-quality bioactive compounds at GMP grade and lower costs for dual purposes – IBD prevention and treatment in relevance to the food as well as the pharmaceutical industries.

EU-OPENSCREEN (EU-OS), the European Research Infrastructure of Open Screening Platforms for Chemical Biology, builds a distributed organization of national screening and chemistry facilities, a common database, and a central headquarter that manages the joint compound collection and coordinates project flow and training. It provides world-class services to academia and industry in the fields of small molecule screening and medicinal chemistry. EU-OS developed its concept and business plan during the preparatory phase and has received information on the Commission Implementing Decision on setting up the EU-OS European Research Infrastructure Consortium (EU-OS-ERIC) in March 2018. In 2018, EU-OS will start its ERIC operations with seven founding members and one observer. EU-OS will promote the rich chemical knowledge of Europe and enabling systematic studies of the bioactivities of a larger collection of compounds leading to ground-breaking insights into cellular and organismal metabolic or signalling pathways. After careful consideration of IPR from all stakeholders involved, all results will eventually become available to the public. EU-OS will thereby also play an increasingly important role in facilitating the drug discovery process in Europe. In addition, it also has a great potential for innovative development of biomarkers and other diagnostics. By carefully considering the recommendations of the Long-term Sustainability Action Plan of the EC and ESFRI, EU-OS will utilize EU-OS-DRIVE to specifically promote measures for i) widening awareness of academia and industry for its services and data, ii) growing capacity and competence in its field across Europe, and iii) completing the management processes needed for a large distributed infrastructure. EU-OS-DRIVE will further help the EU-OS-ERIC to deliver its added-value via constant re-use of generated data and tools by users across the globe and to support the competitiveness of European life science industries.

There has never been a greater need for skilled managers and operators of research infrastructure (RI). Europe must develop the workforce that will turn ~50 nascent RIs with sites in different countries into powerhouses of support for major projects comparable to understanding the blueprint of life or discovering new subatomic particles. RItrain will develop a flagship training programme enabling RIs across all domains to gain expertise on governance, organisation, financial and staff management, funding, IP, service provision and outreach in an international context. It will be designed and delivered by experts who have set up and managed RIs from concept to maturity. We will define competencies required by RIs through consultation with their senior managers. The resulting competency framework will underpin a Bologna-compliant degree, the Master in Research Infrastructure Management, with three delivery routes. (1) Professionals working in RIs (or organisations representing them) can dip into the content, focusing on areas where there is most need. (2) Management teams can take the course as an organisation, dividing modules between them to gain a certificate for the RI. This will flag the RI as an organisation that values staff development, improving its attractiveness as an employer. (3) Recent graduates and others wishing to enhance their employability can take a full master’s degree. Course content will include webinars led by senior managers of RIs. A staff-exchange programme will catalyse exchange of best practice and foster cooperation to develop a mobile work force effective across many RIs. By the end of the project we will be delivering a master’s curriculum funded through course fees. Others with an interest in adopting it will be encouraged to do so, providing a means of expanding the programme. Europe’s research community and global collaborators will gain from world-class facilities to support excellent, high-impact research to benefit humankind.